Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Activation of Drosophila melanogaster TRPA1 isoforms by citronellal and menthol

Brett Boonen
,
Justyna B. Startek
ORCID logo ,
Alina Milici
,
Alejandro López-Requena
ORCID logo ,
Melissa Beelen
,
Patrick Callaerts
ORCID logo ,
Karel Talavera
*
Version 1 : Received: 1 September 2021 / Approved: 3 September 2021 / Online: 3 September 2021 (10:35:49 CEST)

A peer-reviewed article of this Preprint also exists.

Boonen, B.; Startek, J.B.; Milici, A.; López-Requena, A.; Beelen, M.; Callaerts, P.; Talavera, K. Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol. Int. J. Mol. Sci. 2021, 22, 10997. Boonen, B.; Startek, J.B.; Milici, A.; López-Requena, A.; Beelen, M.; Callaerts, P.; Talavera, K. Activation of Drosophila melanogaster TRPA1 Isoforms by Citronellal and Menthol. Int. J. Mol. Sci. 2021, 22, 10997.

Abstract

The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca2+ imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) > dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) > dTRPA1(D) > dTRPA1(C) > dTRPA1(B) for menthol. Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.

Keywords

TRPA1; Drosophila melanogaster; isoform; citronellal; menthol; AITC; HC-030031; repellent; avoidance; olfaction

Subject

Biology and Life Sciences, Anatomy and Physiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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